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天麻素通过调节大鼠纹状体中的兴奋性氨基酸转运体(EAATs)和N-甲基-D-天冬氨酸(NMDA)受体减轻抽动秽语综合征。

Gastrodin Attenuates Tourette Syndrome by Regulating EAATs and NMDA Receptors in the Striatum of Rats.

作者信息

Sun Xueran, Zhang Xin, Jiang Keyu, Wu Min

机构信息

Department of Traditional Chinese Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

出版信息

Neuropsychiatr Dis Treat. 2021 Jul 12;17:2243-2255. doi: 10.2147/NDT.S305925. eCollection 2021.

Abstract

PURPOSE

This study explored whether gastrodin (Gas) could attenuate the symptoms of Tourette syndrome(TS) via the regulation of glutamate (Glu), its transporters (EAAT1 and EAAT2) and its receptors (NMDAR1, NMDAR2A and NMDAR2B) in rats.

MATERIALS AND METHODS

Seventy-five Wistar male rats were randomly divided into five groups (n=15 each): the control, TS, Tia (tiapride, 25mg/kg), Gas60 (gastrodin, 60mg/kg) and Gas120 groups (gastrodin, 120mg/kg). Rats in all groups except the control group received intraperitoneal injection of 3,3'-iminodipropionitrile (IDPN) for 7 consecutive days to establish the TS model. Thereafter, rats in the Tia, Gas60, and Gas120 groups were gavaged with 25mg/kg Tia, 60mg/kg Gas and 120mg/kg Gas for 28 days. Rats in the control and TS groups were gavaged with 0.9% normal saline. Behavioral evaluation was performed by using stereotypy scoring, nodding experiment and autonomic activity test. The Glu level was measured by UPLC-QqQ-MS analysis. The expression of EAAT1, EAAT2, NMDAR1, NMDAR2A and NMDAR2B was measured by Western blot and quantitative real-time PCR (qRT-PCR) analyses.

RESULTS

The results showed that rats with IDPN-induced TS exhibited an increase in stereotypy score, nodding numbers, number of times to enter the central area and autonomic total distance, which could be improved by Tia and Gas treatments. Furthermore, Tia and Gas treatments significantly decreased the IDPN-induced the increase in Glu levels in rats with TS. Furthermore, the decreased expression of EAAT1 and EAAT2 and increased expression of NMDAR1, NMDAR2A, and NMDAR2B in rats with TS induced by IDPN could be substantially altered by Tia and Gas treatments.

CONCLUSION

Gas ameliorated the behavioral dysfunction of rats with TS by maintaining Glu at a normal level, upregulating the expression of EAAT1 and EAAT2, and downregulating the expression of NMDAR1, NMDAR2A and NMDAR2B.

摘要

目的

本研究探讨天麻素(Gas)是否可通过调节大鼠体内谷氨酸(Glu)、其转运体(EAAT1和EAAT2)及其受体(NMDAR1、NMDAR2A和NMDAR2B)来减轻抽动秽语综合征(TS)的症状。

材料与方法

75只雄性Wistar大鼠随机分为五组(每组n = 15):对照组、TS组、泰必利组(泰必利,25mg/kg)、Gas60组(天麻素,60mg/kg)和Gas120组(天麻素,120mg/kg)。除对照组外,其余各组大鼠连续7天腹腔注射3,3'-亚氨基二丙腈(IDPN)以建立TS模型。此后,泰必利组、Gas60组和Gas120组大鼠分别灌胃给予25mg/kg泰必利、60mg/kg天麻素和120mg/kg天麻素,持续28天。对照组和TS组大鼠灌胃给予0.9%生理盐水。通过刻板行为评分、点头实验和自主活动测试进行行为评估。采用超高效液相色谱-串联四极杆质谱(UPLC-QqQ-MS)分析测定Glu水平。通过蛋白质免疫印迹法(Western blot)和定量实时聚合酶链反应(qRT-PCR)分析测定EAAT1、EAAT2、NMDAR1、NMDAR2A和NMDAR2B的表达。

结果

结果显示,IDPN诱导的TS大鼠刻板行为评分、点头次数、进入中央区域次数和自主活动总距离增加,泰必利和天麻素治疗可改善这些症状。此外,泰必利和天麻素治疗显著降低了IDPN诱导的TS大鼠Glu水平的升高。此外,IDPN诱导的TS大鼠中EAAT1和EAAT2表达降低以及NMDAR1、NMDAR2A和NMDAR2B表达增加,可通过泰必利和天麻素治疗得到明显改变。

结论

天麻素通过将Glu维持在正常水平、上调EAAT1和EAAT2的表达以及下调NMDAR1、NMDAR2A和NMDAR2B的表达,改善了TS大鼠的行为功能障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437c/8286077/c3013a3aee49/NDT-17-2243-g0001.jpg

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